Activity of the Hypothalamic-pituitary-adrenal Axis in Different Obesity Phenotypes

Subjects with abdominal obesity are characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a condition of 'functional hypercortisolism'. This appears to be the result of two distinct mechanisms. The first, which appears to be central in origin, is characterized by altered ACTH pulsatile secretory dynamics and by hyper-responsiveness of the HPA axis to different neuropeptides and acute or chronic stress events and, possibly, to selected dietary factors. The other appears to be located in the periphery, specifically the liver and visceral adipose tissue, and is characterized by supranormal cortisol production, whose paracrine and systemic effects remain unclear. It is suggested that increased exposure to cortisol of the body may play a fundamental role not only in the development of increased fat in abdominal/visceral depots, but also in determining all metabolic abnormalities closely related to the abdominal obesity phenotype.